Vitamin C transiently arrests cancer cell cycle progression in S phase and G2/M boundary by modulating the kinetics of activation and the subcellular localization of Cdc25C phosphatase
Φόρτωση...
Ημερομηνία
Συγγραφείς
Thomas, C. G.
Vezyraki, P. E.
Kalfakakou, V. P.
Evangelou, A. M.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
J Cell Physiol
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Regulation of cell cycle progression involves redox (oxidation-reduction)-dependent modification of proteins including the mitosis-inducing phosphatase Cdc25C. The role of vitamin C (ascorbic acid, ASC), a known modulator of the cellular redox status, in regulating mitotic entry was investigated in this study. We demonstrated that vitamin C inhibits DNA synthesis in HeLa cells and, mainly the form of dehydroascorbic acid (DHA), delays the entry of p53-deficient synchronized HeLa and T98G cancer cells into mitosis. High concentrations of Vitamin C caused transient S and G2 arrest in both cell lines by delaying the activation of the M-phase promoting factor (MPF), Cdc2/cyclin-B complex. Although vitamin C did not inhibit the accumulation of cyclin-B1, it may have increased the level of Cdc2 inhibitory phosphorylation. This was achieved by transiently maintaining Cdc25C, the activator of Cdc2, both in low levels and in a phosphorylated on Ser216 inactive form that binds to 14-3-3 proteins contributing thus to the nuclear exclusion of Cdc25C. As expected, vitamin C prevented the nuclear accumulation of Cdc25C in both cell lines. In conclusion, it seems that vitamin C induces transient cell cycle arrest, at least in part, by delaying the accumulation and the activation of Cdc25C.
Περιγραφή
Λέξεις-κλειδιά
Antioxidants/pharmacology, Ascorbic Acid/*pharmacology, Cell Cycle/*drug effects, Cell Cycle Proteins/*metabolism, Cell Line, Tumor, DNA/antagonists & inhibitors/biosynthesis, Enzyme Activation/drug effects, G2 Phase/*drug effects, HeLa Cells, Humans, Kinetics, Mitosis/*drug effects, Models, Biological, S Phase/*drug effects, cdc25 Phosphatases/*metabolism
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/15887239
http://onlinelibrary.wiley.com/store/10.1002/jcp.20405/asset/20405_ftp.pdf?v=1&t=h0c6japx&s=34c2a57cbace42707143596ce9f283f2a7cfacfd
http://onlinelibrary.wiley.com/store/10.1002/jcp.20405/asset/20405_ftp.pdf?v=1&t=h0c6japx&s=34c2a57cbace42707143596ce9f283f2a7cfacfd
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής